Reverse transcription is a common feature of retrovirus replication. Viral replication requires a virally encoded reverse transcriptase to generate DNA copies of viral sequences by reverse transcription of the viral RNA genome. Reverse transcriptase, therefore, is a clinically relevant target for the chemotherapy of retroviral infections because the inhibition of virally encoded reverse transcriptase would interrupt viral replication.
An extremely promising and active area of research is in the discovery of non-nucleoside HIV reverse transcriptase inhibitors. Quinazolinones represent a class of compounds which have been found to be useful non-nucleoside based inhibitors of HIV reverse transcriptase. Commonly assigned U.S. patent application Ser. No. 09/056,820 discloses the novel quinazolinone (-)-6-Chloro-4-cyclopropylethynyl-4-trifluoromethyl-3,4-dihydro-2(1H)-quin azolinone as a particularly active non-nucleoside inhibitor of HIV reverse transcriptase with efficacy against HIV reverse transcriptase resistance.
(-)-6-Chloro-4-cyclopropylethynyl-4-trifluoromethyl-3,4-dihydro-2(1H)-quina zolinone is represented structurally as formula (I): ##STR1##
Solvate and crystalline forms of (I) have not been known to exist previously. The discovery of such forms which exhibit chemical and physical advantages for manufacture, purification, and formulation are necessary for feasible commercialization of (I).
Treatment or prevention of the foregoing disorders is accomplished by administering a therapeutically effective amount of the solvate or crystalline form of compound (I) to a human or animal subject in need of such treatment or prevention. Treatment with such forms of compound (I) may be accomplished by its use as a single compound, as a pharmaceutical composition ingredient, or in combination with other antivirals, immunomodulators, antibiotics and vaccines. The compound may be administered enterally or parenterally in solid or liquid dosage forms.